The abilities of various steroids to inhibit sterol synthesis and to depress the level of 3-hydroxy-3-methylglutaryl coenzyme A in cultures of mouse liver cells and in cultured fibroblasts will be investigated in order to determine structural requirements for inhibitory activity. The cellular uptake of certain inhibitory steroids and their interactions with soluble proteins and with subcellular organelles will be studied in an effort to define the mechanisms of their inhibitory action. The effects of altering the amount and kind of sterol in the membrances of L cell cultures upon the transport of certain low molecular weight compounds upon the synthesis of DNA , RNA, and proteins, and upon the activities of certain membrane-bound enzymes (e.g., adenyl cyclase and ATPase) will be examined in an effort to explain the cessation of growth observed in the presence of steroids that inhibit sterol synthesis. Regulation of sterol synthesis in transformed and untransformed mouse embryo-cell cultures will be compared.